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Title: Development of a functional salivary gland tissue chip with potential for high-content drug screening.

Authors: Song, Yuanhui; Uchida, Hitoshi; Sharipol, Azmeer; Piraino, Lindsay; Mereness, Jared A; Ingalls, Matthew H; Rebhahn, Jonathan; Newlands, Shawn D; DeLouise, Lisa A; Ovitt, Catherine E; Benoit, Danielle S W

Published In Commun Biol, (2021 Mar 19)

Abstract: Radiation therapy for head and neck cancers causes salivary gland dysfunction leading to permanent xerostomia. Limited progress in the discovery of new therapeutic strategies is attributed to the lack of in vitro models that mimic salivary gland function and allow high-throughput drug screening. We address this limitation by combining engineered extracellular matrices with microbubble (MB) array technology to develop functional tissue mimetics for mouse and human salivary glands. We demonstrate that mouse and human salivary tissues encapsulated within matrix metalloproteinase-degradable poly(ethylene glycol) hydrogels formed in MB arrays are viable, express key salivary gland markers, and exhibit polarized localization of functional proteins. The salivary gland mimetics (SGm) respond to calcium signaling agonists and secrete salivary proteins. SGm were then used to evaluate radiosensitivity and mitigation of radiation damage using a radioprotective compound. Altogether, SGm exhibit phenotypic and functional parameters of salivary glands, and provide an enabling technology for high-content/throughput drug testing.

PubMed ID: 33742114 Exiting the NIEHS site

MeSH Terms: Acinar Cells/drug effects*; Acinar Cells/metabolism; Acinar Cells/radiation effects; Animals; Calcium Signaling/drug effects; Cells, Cultured; Drug Evaluation, Preclinical*; Female; High-Throughput Screening Assays*; Humans; Hydrogels; Male; Mice, Inbred C57BL; Microbubbles; Middle Aged; Parotid Gland/drug effects; Parotid Gland/metabolism; Parotid Gland/radiation effects; Phenotype; Polyethylene Glycols/chemistry; Radiation Injuries/etiology; Radiation Injuries/metabolism; Radiation Injuries/prevention & control*; Salivary Glands/drug effects*; Salivary Glands/metabolism; Salivary Glands/radiation effects; Tissue Array Analysis*; Xerostomia/etiology; Xerostomia/metabolism; Xerostomia/prevention & control*

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